Development of a Drosophila-based platform to replace and reduce animal experimentation in epilepsy research

Epilepsy is a debilitating and potentially lethal human condition that affects ~1% of the population. The associated costs of care for patients make it the second neurological condition in terms of burden to the NHS. 

Moreover, the epilepsy field is currently being transformed by the impact of genomic studies that are revealing the genetic underpinnings of rare congenital epilepsies often co-morbid with ataxic and sleep disturbances. The large number of candidate loci identified by such studies clearly necessitates the generation of corresponding animal models to confirm the causal connection between mutations in such genes and epileptic seizures. In epilepsy research this almost invariably means rodents.

Drosophila is an ideal organism to test the influence of gene variants on a neurological condition, including polygenic conditions. However, the fly is under-utilized in epilepsy research.

In this application we plan to overcome the obstacles to a full uptake of Drosophila as an alternative and 3Rs-beneficial model for studying epilepsy. Specifically, our scientific aims will be:
1) To develop a methodology for confidently assessing seizures in adult flies. This will include hardware and software development for bioassays to analyse behaviour and neural activation in seizures.
2) To provide proof of principle studies that validate the use of this methodology. This will include analysis of Epg5-Snap25 interactions, of genes linked to Kcna1 and that may ameliorate seizures in Dravet syndrome and generalised epilepsy with febrile seizures, as well as testing ~10 candidate genes identified in human studies by collaborating clinical geneticists.

Through collaboration with project partners and supporting top UK clinical epilepsy genetics, and through a number of pro-active dissemination activities, we aim to facilitate the uptake of flies in epilepsy research, at least to the same level in which they are used in neurodegeneration research.

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Project grant

Status:

Not yet active

Principal investigator

Dr Manolis Fanto

Institution

King's College London

Co-Investigator

Dr James Jepson
Dr Gabriele Lignani

Grant reference number

NC/V001051/1

Award date:

Aug 2020 - Jul 2022

Grant amount

£259,100